Guidance for medicine developers and companies on COVID-19

EMA encourages developers of potential vaccines or treatments for COVID-19 to contact EMA as soon as possible to discuss their strategy for evidence-generation.

They should email their proposals to 2019-ncov@ema.europa.eu.

Depending on the maturity of development, EMA will set up initial discussions on suitable mechanisms to fast-track development and approval, with priority given to the most relevant proposals.

Establishing contact early in the development process is important for ensuring that developers can submit well-prepared applications and make use of the accelerated procedures EMA has put in place for COVID-19 treatments and vaccines.

Guidance is available for developers of potential COVID-19 treatments and vaccines on the rapid review procedures EMA has put in place to speed up development and approval:

• EMA initiatives for acceleration of development support and evaluation procedures for COVID-19 treatments and vaccines

These rapid procedures can accelerate every step of the regulatory pathway while ensuring that robust evidence on efficacy, safety and quality is generated to support scientific and regulatory decisions.

They are available for initial marketing authorisation applications and extension applications for authorised medicines that are being repurposed for the treatment of COVID-19.

Overview of rapid procedures

EMA is ready to apply further flexibility, where it is established that shortening of any other procedural step could have an important public-health impact in dealing with the COVID-19 pandemic.

In addition, EMA will substantially accelerate the linguistic review process for procedures related to COVID-19.

It will also keep the European Commission informed about COVID-19-related applications to help speed up decisions on authorisations.

Other development-support and early-access mechanisms

Medicine and vaccine developers may also consider other regulatory mechanisms to receive enhanced support during medicine or vaccine development, or to enable early patient access to potential treatments or vaccines, including:

• the PRIME scheme (predominantly suitable for treatments and vaccines in earlier stages of development);
• the conditional marketing authorisation procedure;
• compassionate use programmes.

EMA's Committee for Medicinal Products for Human Use (CHMP) is urging the EU research community to pritoritise large randomised controlled clinical studies as these are most likely to generate the conclusive evidence needed to enable rapid development and approval of potential COVID-19 treatments. The CHMP also emphasises the need to include all EU countries in these trials:

• CHMP statement: A call to pool EU research resources into large-scale, multi-centre, multi-arm clinical trials against COVID-19

Advice to sponsors of COVID-19 clinical trials in the EU is in included in the guidance on clinical trial management during the pandemic:

• Good clinical practice: Guidance on clinical trial management during the COVID-19 pandemic

EMA is currently engaging with stakeholders who can further support the conduct of COVID-19 clinical trials across Europe.

For information on ongoing COVID-19 clinical trials in the EU, see Treatments and vaccines for COVID-19: Information on ongoing clinical trials in the EU.

Update: EMA is encouraging collaboration between researchers on high-quality, multi-centre observational studies in the context of COVID-19, and transparency about study protocols and results.

High-quality observational research of real-world data can complement the results of randomised clinical trials in providing evidence on the safety and effectiveness of vaccines and treatments for COVID-19. Such research is also critical for understanding how exposure to certain medicines can affect the risk or the severity of COVID-19.

Researchers should adhere to existing guidelines on the appropriate design and conduct of pharmacoepidemiological studies in order to generate reliable and reproduceable evidence, including the Guide on methodological standards in pharmacoepidemiology developed by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP).

To facilitate collaboration between researchers and to help improve the size and methodological rigour of studies, ENCePP has set up a dedicated COVID-19 response group. For more information on the group's activities, see its mandate on the ENCePP website.

In addition, recommendations on conducting high-quality research during the pandemic are available in an article published by EMA staff and EU researchers on 5 May 2020:

• Pharmacoepidemiology and Drug Safety: Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic

EMA and ENCePP are encouraging researchers to register their pharmacoepidemiological studies (and make study protocols and reports public) in the European Union electronic register of post-authorisation studies (EU PAS Register). They should include ‘COVID-19’ in the study title to allow easy retrieval of their studies.

Guidance is available for clinical-trial sponsors on how they should adjust the management of clinical trials and participants during the COVID-19 pandemic. This covers concrete changes and protocol deviations for dealing with extraordinary situations, such as the need for isolating participants, limited access to public spaces and the reallocation of healthcare professionals:

• Good clinical practice: Guidance on clinical trial management during the COVID-19 pandemic

Guidance is also available on the actions that sponsors of affected clinical trials should take to help ensure the integrity of their studies and the interpretation of the study results while safeguarding the safety of trial participants as a first priority:

• Implications of coronavirus disease (COVID-19) on methodological aspects of ongoing clinical trials

In line with this guidance, EMA will be flexible and pragmatic during the assessment of affected clinical trial data submitted to the Agency as part of marketing authorisation applications.

Guidance is available for companies responsible for human medicines on adaptations to the regulatory framework to address challenges arising from the COVID-19 pandemic, with a particular focus on crucial medicines for use in COVID-19 patients:

• Notice to stakeholders: Questions and answers on regulatory expectations for medicinal products for human use during the COVID-19 pandemic

The guidance covers:

• marketing authorisation and regulatory procedures;
• the manufacturing and importation of active substances and finished products;
• quality variations;
• labelling and packaging requirements;
• good manufacturing practice (GMP) and good distribution practice (GDP) certificates and inspections;
• pharmacovigilance, including submitting individual case safety reports (ICSR) to EudraVigilance.

Companies should note that some of the measures described in the guidance are reserved for crucial medicines used for treating COVID-19 patients.

The guidance was agreed by EMA, the European Commission, the European medicines regulatory network and endorsed by the EU Executive Steering Group on Shortages of Medicines Caused by Major Events. 

Additional guidance is available for marketing authorisation holders on submitting COVID-19-related ICSRs to EudraVigilance, including on the correct use of COVID-19-related terms of version 23.0 of the Medical Dictionary for Regulatory Activities (MedDRA):

• Detailed guidance on ICSRs in the context of COVID-19: Validity and coding of ICSRs